Objective: To analyze the expression of tight junction protein 3(claudin-3) in colorectal cancer and its relationship with the development, metastasis and prognosis of colorectal cancer. Methods: From February 2013 to February 2015, 78 patients with colorectal cancer operated in the People's Hospital of Sanmen County were selected in this study.The tissues of colorectal cancer and adjacent tissues were collected and claudin-3 expression was detected.The relationship between claudin-3 and clinicopathological features of colorectal cancer was analyzed. Results: The positive rate of claudin-3 in cancer tissues(83.33%) was higher than that in paracancerous tissues(48.72%), and the difference was statistically significant(χ²=20.832, P<0.01). The positive rate of claudin-3 in the poorly differentiated group(100.00%) was significantly higher than that in the well-differentiated group(85.71%) and the well-differentiated group(52.63%)(χ²=19.209, P<0.01). The claudin-3 positive rate with lymphatic metastasis(97.30%) was higher than that without lymphatic metastasis(70.73%), and the difference was statistically significant(χ²=9.882, P<0.01). The claudin-3 positive rate in patients with less than 3 years of survival (91.11%) was higher than that in patients with more than 3 years of survival(72.73%)(χ²=4.633, P<0.05). Conclusion The expression of claudin-3 is related to the occurrence, development and lymphatic metastasis of colorectal cancer, and can predict the prognosis of the patients.